Substance abuse and dependence remain alarming social and health concerns in the U.S. and the world. The successful development of treatment medications that are readily accessible and support patient compliance must be based on a clear understanding of the mechanisms of action underlying the effects of abused drugs and the progression to addiction, as well as the development and validation of new chemical moieties with promise as medications. In this competing renewal, we propose to train two pre- and two postdoctoral fellows in the pursuit of these goals. The NIDA Training Program at the University of Texas Medical Branch (UTMB) has been funded since 1994 and has trained a total of 14 pre- and 11 post-doctoral fellows who utilize their knowledge for basic, clinical and translational research, teaching and/or clinical care in academic or industrial settings. The Training Program is supported within the exemplary UTMB infrastructure and graduate programs, under the UTMB Center for Addiction Research umbrella, and benefits from the recruitment of a concentration of faculty and chemists in the new UTMB Program in Chemical Biology. The interdisciplinary interests of the 21 Program Faculty from multiple departments span basic and translational initiatives, including the neurobiology of amino acids, monoamines and neuro-modulators, their roles in the biological effects of abused drugs and the progression to addiction;drug discovery and medications development in addiction, pain management and infectious disease;fetal exposure to medications during pregnancy in opiate addicts;HIV/AIDS associated neuropathy and interactions between HIV and drug addiction. The Program will provide exemplary opportunities for research training within clusters of transdisciplinary collaborations on questions in addiction and offers an attractive, challenging curriculum. Given the growing interest in translational research, a new goal of the Training Program is to provide opportunities for exposure to clinical research and translational thought. A wider appreciation for addiction specific issues will be fostered through journal clubs, workgroups, seminars, and opportunities to interact with experts in the research, treatment and prevention arenas. Laboratory and didactic training will be augmented by program activities that develop the professional skills needed for advancement towards an independent career. The culmination of our efforts is the success of our trainees as complete, contemporary scientists equipped with the tools to advance the mechanistic understanding of addiction and move these advances toward new therapeutic approaches to its treatment. Few effective, accessible medications for the treatment of substance abuse and dependence are currently available. Through clinical and laboratory methods, we will train the next generation of young investigators dedicated to uncover mechanisms underlying chemical dependency and develop new therapeutic medications for treatment.